Tocilizumab Successfully Treats COVID-19 in Patient With Myeloma

The oncology supportive care agent tocilizumab (Actemra) successfully treated COVID-19 in a patient with multiple myeloma, according to a case study from Wuhan, China, published in Blood Cancers.^1,2

The investigators specifically concluded that their research suggests that tocilizumab might effectively treat cytokine storm caused by COVID-19, and that this benefit could potentially be extrapolated to patients with other blood cancers. Cytokine storm is a type of severe immune overreaction that can cause life-threatening respiratory complications.

"Our patients with hematologic malignancies are immunosuppressed, which may put them at higher risk for novel coronavirus infection. What are the characteristics of COVID-19 in patients with blood cancers? What is the optimal treatment approach? Everything is unknown, and that was the motivation for this study," the study’s lead author Changcheng Zheng, MD, of the University of Science and Technology of China, said in a press release.

In the patient with multiple myeloma, tocilizumab successfully resolved COVID-19 symptoms after standard treatments failed, and he was able to be released from the hospital. Zheng emphasized that the patient did not have the standard COVID-19 symptoms of cough and fever, suggesting that patients with hematologic malignancies may not typically have these clinical symptoms of the coronavirus.

Going forward, Zheng is hopeful that the success of tocilizumab in this patient can be a model across hematologic malignancies, but cautions that much more research is still needed.

The case study involved a 60-year-old male with multiple myeloma diagnosed in 2015. He was receiving maintenance therapy for myeloma at the time of his hospitalization on February 1, 2020, for chest tightness and shortness of breath. He tested positive at the time for COVID-19 that was considered severe, despite not having the standard symptoms of cough or fever.

Antiviral and corticosteroid therapies were initially used but did not completely resolve his symptoms. A chest CT scan done on his second day of hospitalization revealed that there were ground glass opacities in his lungs, a characteristic of pneumonia. Additionally he had high levels of the proinflammatory cytokine IL-6.

The patient received 8 mg/kg of tocilizumab (IV, administered 1 time) on day 9 in the hospital, which was day 24 of his having COVID-19. The patient’s IL-6 levels went down after the single intravenous dose of tocilizumab, continuing to decrease over the next 10 days (121.59 to 20.81 pg/mL). The levels then started to increase rapidly, peaking at 317.38 pg/mL, but eventually settled to 117.10 pg/mL.

“The transient rebounding of the IL-6 level to the peak does not mean COVID-19 relapse: instead, this might be attributed to the recovery of the normal T cells,” Zheng et al explained in the article.

His chest tightness resolved 3 days after initiating tocilizumab and on his 19th day in the hospital, a CT scan showed an obvious decrease in the range of ground-glass opacities. On March 13, 2020, the hospital considered the patient to be cured and he was discharged. He also showed no symptoms of multiple myeloma and had normal laboratory results.

The FDA recently approved the initiation of a double-blind, randomized phase III clinical trial of tocilizumab for use in combination with standard of care for the treatment of hospitalized adult patients with severe COVID-19 pneumonia, according to Genentech (Roche), the manufacturer of the interleukin-6 receptor antagonist.³

Genentech is collaborating with the Biomedical Advanced Research and Development Authority (BARDA), a part of the US Health and Human Services Office of the Assistant Secretary for Preparedness and Response (ASPR), to evaluate tocilizumab combined with standard of care versus placebo plus standard of care.

Enrollment is expected to start soon, with a target accrual of 330 patients across the United States and other countries. Investigators will follow patients for 60 days after randomization and early proof of efficacy will be assessed at an interim analysis. Key study endpoints will be clinical status, mortality, mechanical ventilation, and intensive care unit variables.

As the CAR T-cell therapy revolution has spread across the treatment paradigm for patients with hematologic malignancies, tocilizumab has become critical to ensuring that patients are able to receive this type of therapy. Specifically, tocilizumab is approved by the FDA for the treatment of cytokine release syndrome (CRS) that is severe or life-threatening. CRS is the most severe toxicity associated with CAR T-cell therapy. Tocilizumab is used in adults and children aged 2 years and older who have CRS caused by CAR T-cell therapy.

Tocilizumab has been a critical component to ensuring the success of several pivotal clinical trial of CAR T-cell therapy. For example, the FDA is currently reviewing a biologics license application for the anti-CD19 CAR T-cell therapy lisocabtagene maraleucel for the treatment of adult patients with relapsed/refractory large B-cell lymphoma after at least 2 prior therapies, based on data from the multicenter phase I TRANSCEND NHL 001 study.⁴ In this pivotal trial, the incidence of any grade CRS was 42%, which occurred at a median onset of 5 days. Nineteen percent of patients received tocilizumab to manage CRS. Nearly all cases of CRS were entirely reversible.

Another oncology drug, ruxolitinib (Jakafi), is being explored in the planned phase III RUXCOVID trial as a treatment for cytokine storm in patients with COVID-19. The RUXCOVID trial will specifically evaluate the JAK1/2 inhibitor in combination with standard of care treatment versus standard of care alone in patients with severe COVID-19 pneumonia caused by SARS-CoV-2 infection.

Novartis and Incyte, the covdevelopers of ruxolitinib, decided to launch the trial based on preclinical and preliminary clinical findings indicating ruxolitinib could lower the number of patients with these complications who need intensive care and mechanical ventilation. In a press release, the companies reported that they plan to initiate a compassionate use program for patients with COVID-19 to have access to ruxolitinib.⁵

References

1. Case Study: Treating COVID-19 in a Patient with Multiple Myeloma. Published online April 3, 2020. https://prn.to/2JzIakv. Accessed April 3, 2020.
2. Zhang X, Song K, Tong F, et al. First case of COVID-19 in a patient with multiple myeloma successfully treated with tocilizumab. Blood Adv. 2020;4(7):1307-1310. https://doi.org/10.1182/bloodadvances.2020001907
3. Genentech Announces FDA Approval of Clinical Trial for Actemra to Treat Hospitalized Patients With Severe COVID-19 Pneumonia. Posted March 23, 2020. https://www.gene.com/media/press-releases/14843/2020-03-23/genentech-announces-fda-approval-of-clin. Accessed March 23, 2020.
4. U.S. Food and Drug Administration (FDA) Accepts for Priority Review Bristol-Myers Squibb’s Biologics License Application (BLA) for Lisocabtagene Maraleucel (liso-cel) for Adult Patients with Relapsed or Refractory Large B-Cell Lymphoma. Published February 13, 2020. https://bit.ly/39uYC0l. Accessed February 13, 2020.
5. Novartis announces plan to initiate clinical study of Jakavi® in severe COVID-19 patients and establish international compassionate use program. Published April 3, 2020. https://bit.ly/3aHA2dF. Accessed April 3, 2020.

"Tocilizumab was effective in the treatment of COVID-19 in this patient with multiple myeloma, but further prospective and randomized clinical trials are needed to verify the findings," said Zheng.